Vascular endothelial cell (EC) activation is one of the first events in inflammatory conditions and transplant rejection. A specific marker of EC activation is E-selectin. Expression of this gene is generally absent under resting conditions and induced by inflammatory stimuli, as well as being NF-kB dependent. Expression is restricted to the endothelium.
Immunohistochemistry is a standard technique by which signalling events involved in disorders associated with inflammatory, thrombotic, ischaemic or neoplastic conditions or transplant rejection, can be assessed; and, for example, E-selectin expression can be readily studied by this method in vitro. However, monitoring of E-selectin expression in vivo has been limited to immunohistochemistry of biopsies or post-mortem specimens. There has been a need by workers in the art for an in vivo model allowing assessment of E-selectin expression in a live subject.
The present invention relates to an animal model useful for screening potential therapeutic agents for the treatment of disorders associated with inflammatory, thrombotic, ischaemic or neoplastic conditions or prevention of transplant rejection. In particular, the present invention provides a novel model in which endothelial cell activation can be assessed in vivo by a simple and sensitive enzyme assay.